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951.
Gaudet MM Kirchhoff T Green T Vijai J Korn JM Guiducci C Segrè AV McGee K McGuffog L Kartsonaki C Morrison J Healey S Sinilnikova OM Stoppa-Lyonnet D Mazoyer S Gauthier-Villars M Sobol H Longy M Frenay M GEMO Study Collaborators Hogervorst FB Rookus MA Collée JM Hoogerbrugge N van Roozendaal KE;HEBON Study Collaborators Piedmonte M Rubinstein W Nerenstone S Van Le L Blank SV Caldés T de la Hoya M Nevanlinna H Aittomäki K Lazaro C Blanco I Arason A Johannsson OT Barkardottir RB Devilee P 《PLoS genetics》2010,6(10):e1001183
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. 相似文献
952.
The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) is considered responsible for the population declines and extinctions of hundreds of amphibian species worldwide. The panzootic
was likely triggered by human-assisted spread, but once the pathogen becomes established in a given region, its distribution
is probably determined by local drivers. To assess the relative importance of potential drivers of infection in red-spotted
newts (Notophthalmus viridescens), we measured Bd levels in 16 populations throughout central Pennsylvania. Infected individuals were detected in all but four populations,
indicating that Bd is widespread in this region. We quantified local factors hypothesized to influence Bd, and found that infection levels were best predicted by the proportion of the pond substrate consisting of leaf litter or
vegetation, along with a significant effect of water temperature. Bd infection in amphibians is temperature-dependent, and one possible explanation of the apparent substrate effect is that tree
cover and vegetation provide shade, reducing the availability of shallow, warm-water patches in which newts might reduce or
clear Bd infections. Alternatively, leaf litter and emergent vegetation might increase Bd infection more directly, perhaps by providing substrates for environmental growth of the fungus. We also observed a curvilinear
relationship between Bd load and snout-vent length (a proxy for age), hinting that newts might develop acquired resistance to Bd infection. Though correlational, these results add to a growing body of evidence suggesting that environmental temperature
is an important driver of Bd infection dynamics. 相似文献
953.
954.
Thibaud Souter Raphael Cornette Julio Pedraza John Hutchinson Michel Baylac 《Comptes Rendus Palevol》2010,9(6-7):411-422
Geometric morphometrics involves defining landmark points to generate a discrete representation of an object. This crucial step is strongly influenced by the biological question guiding the analysis, and even more when using curve and surface semi-landmarks methods, because these require to generate a template of reference. We exemplify these constraints using two datasets from projects with very different backgrounds. The Theropod Dataset is a functional morphometric analysis of different extinct and extant theropod pelves. The Shrew Dataset is a populational morphometric analysis of the white-toothed shrew with very small variations in skull shape. We propose a novel procedure to generate a regular template configuration, using polygonal modelling tools. This method allows us to control the template geometry and adapt its complexity to the morphological variation in the sample. More studies are necessary to assess the morphometric and statistical importance of template design in curve and surface analyses. 相似文献
955.
Michel Veuille 《Comptes rendus biologies》2010,333(2):145-156
Darwin's book on the Descent of Man and Selection in Relation to Sex (1871) is often viewed as the continuation of TheOrigin of Species published 12 years earlier (1859), both because of the implicit parallelism between natural selection and sexual selection, and because Darwin himself presents the book as developing a subject (man) which he intentionally omitted in the Origin. But the Descent can also be viewed as the continuation of his book on Variation published three years earlier (1868). Firstly because Darwin's hypothesis of pangenesis links the selection process to the origin of variation through use and disuse, an idea underlying his speculations on the origin of moral sense in humans. Second because like the action of the horticulturist on his domestic crops, sexual selection exerted by one sex on the other sex can develop fancy traits that are not easily accounted for by their utility to the selected organism itself, such as artistic taste, pride, courage, and the morphological differences between human populations. These traits are difficult to reconcile with pangenesis. They add up to other contradictions of the book possibly resulting from Darwin's erroneous inference about the mechanism of inheritance, like those on the determination of sex-ratio, or the confusion between individual adaptation and the advantage to the species. These inconsistencies inaugurate a weakening of the Darwinian message, which will last 50 years after his death. They contributed to the neglect of sexual selection for a century. Darwin however maintained a logical distinction between evolutionary mechanisms and hereditary mechanisms, and an epistemological distinction between evolutionary theory and Pangenesis hypothesis. In the modern context of Mendelian genetics, Darwin's sexual selection retrospectively appears as luminous an idea in its pure principle as natural selection, even though the mechanisms governing the evolution of sexual choice in animals remain largely unresolved. 相似文献
956.
Michel Toussaint Anthony J. Olejniczak Pierre Cattelain Claire Letourneux 《Journal of human evolution》2010,58(1):56-67
A human lower right deciduous second molar was discovered in 1984 at the entrance of Trou de l'Abîme at Couvin (Belgium). In subsequent years the interpretation of this fossil remained difficult for various reasons: (1) the lack of taxonomically diagnostic elements which would support its attribution to either Homo (sapiens) neanderthalensis or H. s. sapiens; (2) the absence of any reliable chronostratigraphic interpretation of the sedimentary sequence of the site; (3) the contradiction between archaeological interpretations, which attributed the lithic industry to a transitional facies between the Middle and Early Upper Palaeolithic, and the radiocarbon date of 46,820 ± 3,290 BP obtained from animal bone remains associated with the tooth and the flint tools.Thanks to recent progress regarding these three aspects, the tooth from Trou de l'Abîme may now be studied in detail. Analyses of the morphology and enamel thickness of the fossil yielded diagnostic characters consistent with an attribution to Neandertals. Re-examination of the lithic industry of Couvin shows that it corresponds to the late Middle Palaeolithic rather than a transitional facies. Furthermore, a new analysis of the site stratigraphy indicates that the unit situated above the archaeological layer in which the tooth was found is probably a palaeosol of brown soil type. Comparison with the regional cave sequences as well as with the reference sequence from the Belgian loess belt tends to show that the most recent palaeosol of this type is dated between 42,000 and 40,000 BP. This is consistent with both a recently obtained AMS result at 44,500 BP and the published conventional date. 相似文献
957.
Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5 总被引:1,自引:0,他引:1
Pavri R Gazumyan A Jankovic M Di Virgilio M Klein I Ansarah-Sobrinho C Resch W Yamane A Reina San-Martin B Barreto V Nieland TJ Root DE Casellas R Nussenzweig MC 《Cell》2010,143(1):122-133
Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. 相似文献
958.
959.
Marilisa?Barranca Simona?Fontana Simona?Taverna Giovanni?Duro Isabelle?Zanella-Cleon Michel?Becchi Giacomo?De?Leo Riccardo?AlessandroEmail author 《Biotechnology letters》2010,32(4):565-570
Parietaria judaica pollen is a common cause of airway allergic disease in the Mediterranean area. Proteome analysis of mature Parietaria judaica pollen by two-dimensional gel electrophoresis (2-DE) and mass spectrometry has established the first reference proteome map
of this weed. Proteins involved in a variety of cellular functions as well as the occurrence of allergens were detected. By
using 2-DE and immunoblotting with sera from Parietaria judaica allergic patients we obtained a more detailed characterization of Parietaria judaica allergen profile so to improve our comprehension of the pathogenesis of pollen-induced allergic reaction. 相似文献